The Accepted Marketing Application of Roche's Glofitamab in China

Recently, the marketing application of Roche's Glofitamab has been accepted by NMPA in China, intending to treat the adult patients with recurrent or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma after at least two lines of systematic therapy.

Large B-cell lymphoma is an invasive non-Hodgkin's lymphoma (NHL), one of the most common hematologic tumors. DLBCL is a subtype of large B-cell lymphoma, and its first-line treatment is R-CHOP plan (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone). Although many patients have a response to the first-line treatment, 40% patients have relapsed after the treatment, being willing to a new treatment option urgently.

Roche arranges two CD20/CD3 bispecific antibodies

Glofitamab, developed by Roche, is a 2:1 type T cell bispecific antibody targeting CD20/CD3, that is, it contains 2 Fab arms for binding CD20 (a kind of B cell surface protein expressed in most B-cell malignant tumors) on B cells, and 1 Fab arm for binding CD3 (a part of the T-cell surface receptor) on T cells, which makes Glofitamab gather T cells well and guide them to participate in clearing malignant B cells. To prolong the half-life, Roche designs a Fc region for Glofitamab, canceling the binding of FcγRs and C1q and keeping the binding of FcRn, which has the effect of prolonging the half-life.

A phase I/II study, named as NP30179, proves the efficacy and safety of Glofitamab. 155 DLBCL patients were included in this study, which results showed that 40.0% (62/155) of patients achieved the complete response (CR) and 51.6% (80/155) of patients achieved the objective response (OR, including CR and partial response). 73.1% of the patients achieving CR remained the response 12 months after the end of treatment. The median duration of response is 18.4 months.

The most common adverse event is the cytokine release syndrome (CRS), usually being Class 1/2.

In addition to Glofitamab, Roche has developed another CD20/CD3 bispecific antibody, Mosunetuzumab (Lunsumio). It was approved for marketing by the EU last year for treating the adult patients with recurrent or refractory follicular lymphoma (FL) after at least 2 kinds of systematic therapy. The action mechanism of Mosunetuzumab is to lock the CD20 marker on the malignant B cells and CD3 protein on the T cells, making immune killer cells closer to cancer cells and kill them.

According to the newly released data, Mosunetuzumab induced a high complete response rate in the FL patients after multiple previous treatments, with a good tolerance. Specifically, after 18.3 months of median follow-up time, the median duration of response (mDoR) is 22.8 months, CR is 60% (n=54/90), and objective response rate (ORR) is 80% (n = 72/90). The most common adverse event is the CRS (39%), mostly being Class 2, which subsides at the end of the treatment.